The specific aims of our research are to define mechanisms of gastric acid secretion and gastrointestinal hormone release in humans; to develop and evaluate new methods of measuring gastric function under physiologic conditions in humans; to study pathophysiological defects in patients with peptic ulcer disease; to study the effect of vagotomy in patients with peptic ulcer disease and Zollinger-Ellison syndrome; to develop and study new methods of treating patinets with peptic ulcer; and to evaluate gastric function in patients with diabetes mellitus. To accomplish these goals, gastric acid secretion will be measured by aspiration and by in vivo intragastric titration, a method that allows measurement of acid secretion with food in the stomach. Vagal function will be evaluated by sham feeding normal subjects and patients with ulcer disease. We are also developing methods to measure bicarbonate secretion in humans. Our studies during the past 5 years have led to a number of interesting and we think important questions which we hope to anser during the next grant period. We will study the mechanism by which neural stimulation releases gastrin in man and will evaluate mechanisms controlling food-stimulated gastrin release. We will also determine whether prolonged gastric alkalinization is a stimulus for gastrin synthesis and release. We have shown that endogenous opiates play a physiological role in acid secretion and we plan to study the mechanisms whereby this occurs. Animal studies have suggested that salival contains an acid inhibitory substance. We will determine whether or not this substance exists and plays a physiological role in acid secretion in humans. Pathophysiological studies wll include an evaluation of the increased food-stimulated acid secretory rates and maximal secretory capacity which are characteristic of duodenal ulcer patients. Additional studies will be performed to determine the cause of reduced maximal secretory capacity and increased serum gastrin concentration after vagotomy. We hope to define the natural history of epidemic gastritis with hypochlorhydria. In normal subjects and diabetic patients we will study volume-pressure-gastric emptying relationships. We plan two controlled clinical trials evaluating the role of environmenal stress in the incidence of complications and recurrence of duodenal ulcer.